Shifts of fluids and proteins are exceptionally rapid throughout the fetal body and their distribution is abnormal in many diseases with edema in the fetus and newborn. The lymph system plays a critical role in fluid distribution because it returns fluids and proteins that have been filtered from the blood back into the circulation. Yet the mechanisms regulating fetal lymph flow remain largely unknown. We therefore propose several lines of investiagation to better understand this aspect of physiology. We will study whole body lymph flow responses to: 1) successive infusions of isotonic saline; 2) infusions of hypo-, iso-, and hypertonic saline; 3) infusions of acidic and alkaline solutions, to test pH influence; 4) infusions of different electrolytes and colloids to test the effects of individual substances; and 5) changing blood volume by hemorrhage and volume loading. Experiments will be carried out in acutely prepared fetal lambs in utero to test for mechanisms. They will be repeated in chronically prepared fetal lambs, newborns, and adults to examine the physiologic importance of lymph flow and to measure changes with maturation. Effects of blocking lymph flow will also be done to test its importance to different organs of the body. The experiments will constitute the first systematic study of fetal lymph flow and will shed light on the importance of the lymph system in defending the body against edema.